Research suggests that pesticide exposure has been linked to Parkinson’s disease. Nationally, over 4 million pounds of neonicotinoid pesticides are used annually across 140 to 200 million acres of farmland. Previously, flupyradifurone was shown to induce significant oxidative stress in bees and caspase-3 protein assays, indicating greater apoptosis levels in pesticide-exposed bees. This study investigates similar effects in C. elegans by examining mitochondrial counts and blebbing, an apoptotic marker, in dopaminergic neurons in response to specific pesticides. These would indicate cellular stress and neurodegeneration, hallmarks of Parkinson’s disease. Imidacloprid was selected as it is the most used neonicotinoid in the world, and flupyradifurone since it is meant to replace the increasingly pest resistant neonicotinoids. The antioxidant N-acetyl cysteine (NAC) was added to some pesticide-exposed worms to explore the possibility of reversing the effects of the pesticide-induced oxidative stress. Neuronal blebbing and mitochondria were analyzed using ImageJ software and the Simple Neurite Tracer. The pesticides were found to cause significant blebbing in the dopaminergic neurons of C. elegans. This was surprising because C. elegans and dopaminergic neurons are not the pesticides’ targets. The NAC treatment showed significant recovery from the neurodegeneration. Future experiments will focus on pinpointing the molecular target responsible for degeneration. This may reveal how pesticides contribute to Parkinson’s disease.

This study aims to investigate retinal microglia in Alzheimer’s disease (AD), focusing on phagocytic responses to amyloid-beta (Aβ), pathogenic tau forms, and bacterial infection. Brain microglia dysfunction contribute to AD pathogenesis, however, the phagocytic ability of retinal microglia in AD remains unexplored. We conducted histological analysis on postmortem retinas from patients with AD and mild cognitive impairment (MCI) vs donors with normal cognition (NC). We immunostained for markers of Aβ, tau isoforms, and bacterial antigens, alongside microglial markers, and assessed the total immunoreactive and colocalized area and microglial population. The extent of retinal microgliosis was closely correlated with an increased retinal Aβ42 burden. However, over 80% fewer retinal microglia engaged in Aβ42 internalization in MCI and AD patients compared to NC controls, suggesting impaired Aβ phagocytosis. Retinal microglia were also involved in the phagocytosis of abnormal tau forms, including hyperphosphorylated (p)tau, oligomeric tau and tau aggregates. This phenomenon was less frequent than Aβ uptake and significantly different in AD patients. In response to bacterial infection, retinal microglia often recognized and engulfed infected cells. Yet, the relative microglial population involved in phagocytosis of bacterial-infected cells substantially declined in AD retinas. Despite significantly higher levels of microgliosis, Aβ, tau, and pathogen-infected cells in the AD retina, microglia exhibited impaired phagocytic ability.

Ischemic stroke, which happens due to blocked blood flow to the brain, is a leading cause of long-term adult disability in the United States. Decreased blood flow forms an area of cell death called the stroke infarct. After a stroke, astrocytes proliferate and form a protective barrier between healthy tissue and the stroke infarct and secrete factors that regulate synaptogenesis (formation of new synapses) and axonal sprouting (growth of new neural connections). Post-stroke recovery methods, like physical therapy, have limited effects, calling for alternatives that promote functional recovery. Here, we compare two porous hydrogels designed to increase astrocyte infiltration and axonal sprouting: microporous annealed particle (MAP) hydrogel and MAPcV hydrogel, which combines MAP and clustered vascular endothelial growth factor nanoparticles (CLUVENA). Using immunohistochemistry and Imaris image analysis to visualize and quantify cells, we found that there are more astrocytes in the MAPcV hydrogel. Also, MAPcV has an increased volume of axons that are tightly associated with astrocytes compared to MAP. This suggests that the downstream effects of CLUVENA may influence astrocyte presence, and CLUVENA may make astrocytes more likely to associate with axons. CLUVENA may provide additional benefits for neural recovery if integrated with MAP. Our research will inform us of improved ways to ameliorate the post-stroke environment and ultimately, achieve functional recovery in mice models.

OLM interneurons are hippocampal CA1 cells that express CHRNA2 and selectively inhibit the distal dendrites of CA1 pyramidal neurons. These interneurons disinhibit the proximal dendrites to enhance inputs from CA3 in the Schaffer collateral pathway. When OLM cells were optogenetically activated, they blocked the long-term potentiation (LTP) in the entorhinal synapses and activated LTP in CA3 synapses, proving that OLM interneurons are involved in hippocampal plasticity. Furthermore, OLM cells integrate local neural signaling to create a synchronized control of the CA1 network which is critical for encoding memory. However, the changes in population dynamics of this cell type across learning is still unknown. In order to answer this question, we will be using genetically encoded voltage indicators (GEVIs) on mice trained to navigate a linear treadmill track. After training, the hippocampal inhibitory interneurons will be imaged to see how activity has evolved before and after learning the location of a reward. All the data will then be processed using python and analysed with MATLAB. These findings have significant implications for understanding cognitive diseases with impacted hippocampal activity such as Alzheimer’s disease, autism, and schizophrenia, since interneuron dynamics can provide much needed insight into how inhibitory networks affect the hippocampus in learning-related changes with potential therapeutics that can seek to alleviate these disorders and improve cognitive function by restoring that balance.

Opioids are analgesics with a high risk of addiction, which may be due in part to a user’s motivation to seek relief from an aversive mental state such as withdrawal. Noradrenergic neurons are involved in opioid reward, withdrawal, and food reward, but the extent to which noradrenergic mu-opioid receptors (MORs) impact these circuits is unknown. We sought to determine their significance in mediating natural reward in opioid non-dependent and dependent states. We hypothesized that mice lacking noradrenergic MORs will show more motivation for food compared to wildtype mice during opioid withdrawal. We used operant boxes to perform food self administration experiments. We trained male and female dopamine-beta hydroxylase cre/floxed MOR mice to poke the active hole (AH) to earn a food reinforcer, over three difficulty levels. Next we induced morphine dependence and re-ran the operant boxes once the mice were in withdrawal. We compared differences in motivation pre- and post-withdrawal across sex and genotype, measured by the number of AH pokes and reinforcers gained. Our initial results show a decrease in motivation for Cre+ mice (MOR knockout) and male mice post-morphine, and an increase in motivation for female Cre- (wildtype) mice post-morphine. These results contradict our hypothesis, which may indicate that MORs in other noradrenergic regions are affecting motivation, or that MORs are protective against depressive withdrawal symptoms. We are currently repeating the experiment to increase statistical power.